The Interplay Between Iron Metabolism and Insulin Resistance: A Key Factor in Optimizing Obesity Management in Children and Adolescents

Abstract

Iron plays a vital role in insulin signaling, regulating molecular mechanisms that influence cellular insulin responses. This review explores the link between iron metabolism and insulin resistance (IR) in children and adolescents with obesity. A connection between iron metabolism, iron deficiency (ID), and IR is well-documented, but further longitudinal studies are needed to better understand how iron metabolism influences insulin resistance during childhood and adolescence. This connection warrants attention due to its significant public health implications, as optimizing obesity management could help prevent both ID and metabolic complications in children. Current evidence does not suggest that dietary factors are primary contributors to ID in children. However, there is scientific evidence that weight reduction can restore iron homeostasis in people with obesity. Therefore, efforts should focus on improving dietary habits, increasing awareness of iron's importance, and implementing strategies to address both ID and obesity.

Keywords: childhood obesity; insulin resistance; iron deficiency; nutritional strategies; weight loss.

Figure 1

Search process of studies on iron deficiency, insulin resistance, and nutritional strategies to improve iron status in children and adolescents with obesity.

Figure 2

Iron metabolism and IR are linked by a complex interaction among tissues such as macrophages, the skeleton, adipose tissue, liver, and muscle. High body iron levels in the liver impair insulin signaling pathways, increase oxidative stress, and hinder insulin function. Excess iron in tissues promotes the production of reactive oxygen species (ROS), which activate inflammatory pathways that disrupt glucose uptake. Elevated iron levels can interfere with adipocyte differentiation and lipid metabolism, reducing adiponectin levels. They also promote macrophage inflammation and suppress osteocalcin secretion, which affects adiponectin secretion from adipose tissue. The relationship between iron and insulin resistance is bidirectional: hyperinsulinemia increases iron accumulation, creating a vicious cycle where elevated insulin stimulates ferritin production, leading to iron retention and decreased hepcidin levels, which, in turn, increases iron absorption and retention, worsening iron overload. FFA: free fatty acids.